Sex hormones have since long been known to ameliorate arthritic symptoms in chronic arthritis during pregnancy, see for example Hench P. S. "The ameliorating effect of pregnancy on chronic atrophic arthritis, fibrositis, and intermittent hydrathrosis", Mayo Clin. Proc., 13, 161-167, 1983. The use of oral contraceptives in patients with rheumatoid arthritis (RA) have proven to decrease the incidence of RA, see Wingrave S. J., Kay C. R. "Reduction in incidence of rheumatoid arthritis associated with oral contraceptives", Lancet, 569-571, 1978; and Vandenbroucke J. P. et al., "Oral contraceptives and rheumatoid arthritis: Further evidence for a preventive effect", Lancet 839-842, 1982.
In JP 268575/1990 estradiol derivatives are described, but the substituents in 17-position are completely different from the substituents in 17-position of the present application. The problem underlying the invention described in JP 268575/1990 is to find compounds against osteoporosis, said compounds having an excellent bone resorption inhibiting action without showing side effects such as risk for genital cancer etc. known in the art for estrogens.
The problem underlying the present invention is to develop novel steroidal estrogens with high anti-inflammatory and immunosuppressive effects, but with low "sex hormonal" activities. The steroidal estrogens known in the prior art, have the disadvantages that they influence genital and breast tissues, thereby conferring adverse effects such as endometrial and breast cancers if given in too high amounts.
The problem mentioned above has been solved by developing new steroidal estrogens according to the formula I, as will be described in the following.